Rapid Estimation of Binding Constants for Cucurbit[8]uril Ternary Complexes Using Electrochemistry

Area of Science:

• Supramolecular chemistry
• Electrochemistry
• Materials science

Background:

• Supramolecular complexes are crucial in biomedicine and adaptive materials.
• Accurate binding affinity determination is vital for designing novel drugs and materials.
• Existing methods can be time-consuming or lack precision.

Purpose of the Study:

• To develop a facile and precise electrochemical method for estimating binding constants (K_G2) of cucurbit[8]uril-methyl viologen-based ternary complexes (CB8-MV^2+-G2).
• To establish a reliable correlation between electrochemical properties and binding constants.
• To demonstrate the application of this method for unknown and sparsely soluble complexes.

Main Methods:

• Electrochemical measurements to determine reduction potentials of CB8-MV^2+-G2 ternary complexes.
• Isothermal titration calorimetry (ITC) for reference binding constant determination.
• Linear regression analysis to establish correlation between reduction potential and binding constants.
• Computational and experimental mechanistic investigations.

Main Results:

• A novel electrochemical approach was developed, achieving high precision (±0.03) and accuracy (±0.32) in logK_G2.
• A strong linear correlation (R^2 > 0.8) was found between reduction potential and binding constants for 25 sample complexes.
• Mechanistic studies revealed dynamic host-guest exchange post-electron transfer as the basis for the correlation.
• Binding constants for unknown hydrocarbon-based ternary complexes were successfully estimated.

Conclusions:

• The developed electrochemical method provides a rapid (<10 min) and accurate alternative for determining binding constants of CB8-MV^2+-G2 complexes.
• This method facilitates the design and discovery of novel supramolecular materials and drugs, especially for challenging, sparsely soluble guests.
• The findings highlight the utility of electrochemistry in probing supramolecular interactions and host-guest dynamics.